CTSB p.Asp137=
c.411C>T · rs200926074 · VCV1635211
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.413%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.3 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 9.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.413%
Middle Eastern · 25/6,046 alleles
Filtering AF
0.287%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.246%
Overall
0.0142%
229/1,613,498 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.413% | 242 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,975 |
| Admixed American | 0.03% | 3,334 |
| South Asian | 0.0264% | 3,794 |
| African / African-American | 0.0133% | 7,505 |
| European (non-Finnish) | 0.0109% | 9,146 |
| Finnishnot grpmax-eligible | 0.00314% | 31,865 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CTSB
- Protein
- p.Asp137=
- Coding
- c.411C>T
- MANE Select
- NM_001908
- dbSNP
- rs200926074
- Type
- single nucleotide variant
- Location
- chr8:11849081 (GRCh38)
- Gene constraint
- LOEUF 1.756 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.95 · 21 PDB
- Residue 137
- a disulfide bond; an α-helix
Similar variants
- CTSB p.Arg331Pro Uncertain significance ★★ ⚠ same type
- CTSB p.Asp333Asn Uncertain significance ★★ ⚠ same type
- CTSB p.Lys220Glu Uncertain significance ★★ ⚠ same type
- CTSB p.Met73Thr Uncertain significance ★★ ⚠ same type
- CTSB p.Thr332Ala Uncertain significance ★★ ⚠ same type
- CTSB c.327+20C>T Benign ★★ same type
- CTSB c.446+9G>C Benign ★★ same type
- CTSB c.447-16G>C Benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctsb-p-asp137 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown